Pathogenic point mutations of mitochondrial DNA (mtDNA) are associated with a large number of heterogeneous diseases involving multiple systems with which patients may present with a wide range of clinical phenotypes. In this study, we describe a novel heteroplasmic missense mutation, m.11406T>A, of the ND4 gene encoding the subunit 4 of mitochondrial complex I in a 32-year-old woman with recurrent epileptic seizure, headache and bilateral hearing loss. Skeletal muscle histochemistry demonstrated that approximately 20% of fibers were cytochrome C oxidase (COX) deficient with increased activity of succinate dehydrogenase (SDH). Further investigations in muscle specimens showed significantly reduced level of ND4 protein. It is interesting that the subunits of complex I (ND1 and NDFUB8) and complex IV(CO1) were also remarkably decreased. These findings indicate that ND1, NDFUB8 and CO1 are more susceptible than other subunits to mutations in the mitochondrial ND4 gene.

中文翻译：

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一种新的m.11406T>线粒体ND4基因突变导致MELAS综合征

线粒体 DNA (mtDNA) 的致病性点突变与涉及多个系统的大量异质性疾病相关，患者可能会出现多种临床表型。在这项研究中，我们描述了 ND4 基因的一种新的异质性错义突变，m.11406T>A，编码线粒体复合体 I 的亚基 4，在一名患有复发性癫痫发作、头痛和双侧听力损失的 32 岁女性中。骨骼肌组织化学表明，大约 20% 的纤维缺乏细胞色素 C 氧化酶 (COX)，琥珀酸脱氢酶 (SDH) 的活性增加。对肌肉标本的进一步研究显示 ND4 蛋白水平显着降低。有趣的是，复合物 I（ND1 和 NDFUB8）和复合物 IV（CO1）的亚基也显着减少。